Neuromuscular

IMMUNE MYOPATHY WITH ANTIBODIES TO SIGNAL RECOGNITION PARTICLE

SRP pathology
  Early
  Intermediate
  Late, Severe
  Late, Mild
  Capillaries
  Complement deposition


General features
SRP: EARLY PATHOLOGY
Necrotic & Regenerating muscle fibers: Scattered

H&E stain
Necrotic & Regenerating (Arrow) muscle fibers: Scattered

H&E stain

Acid phosphatase stain

Acid phosphatase stain


H&E stain
Necrotic & Regenerating muscle fibers

Congo red stain


Acid phosphatase stain
Necrotic muscle fibers: Scattered
  Phagocytic cells: Stain for acid phosphatase
  Cytoplasm: Stains for C5b-9 complement

C5b-9 stain


NADH stain
Necrotic (pale) & Regenerating (dark) muscle fibers

NADH stain

MHC Class I
  Muscle fibers
    Generally not expressed
    Present in cytoplasm of regenerating muscle fibers
  Cells: Present on histiocytic cells associated with necrotic muscle fibers
  Vessels: Normall present on endomysial capillary & perimysial vessel endothelial cells

MHC Class I stain

SRP: INTERMEDIATE PATHOLOGY

Muscle fiber sizes: Varied; Small to Upper limit of normal; Bimodal distribution
Small muscle fibers: Rounded; Large nuclei; Basophilic cytoplasm
Endomysial connective tissue: Increased, Mild to Moderate
Pathology distribution: Patchy; Some regions with more small muscle fibers & Increased endomysial connective tissue

H&E stain

Muscle damage
  More severe, with increased endomysial connective tissue, in some regions

H&E stain


H&E stain
Muscle fiber sizes: Bimodal
Small muscle fibers: Rounded; Large nuclei
Endomysial connective tissue: Mildly increased
       
H&E stain

Gomori trichrome stain

Muscle fiber internal architecture
  Some small fibers stain dark
  One necrotic muscle fiber is pale

NADH stain


VvG stain
Fiber sizes: Varied; Small fibers round
Endomysial connective tissue: Increased
Muscle fiber necrosis: Few fibers with pale-stained cytoplasm

Congo red stain


Acid phosphatase stain
Necrotic muscle fibers
  Scattered
  Pale cytoplasm
  Associated histiocytic cells

Acid phosphatase stain
Acid phosphatase positive cells
  Scattered in endomysium

Acid phosphatase stain

C5b-9 Deposition
  Necrotic muscle fibers, Scattered: Cytoplasm
  Endomysial capillaries
  Normally present in: Perimysial, Intermediate-sized Vessels

C5b-9 stain

SRP myopathy: Many muscle fibers persist in immature states

Alkaline phosphatase stain
Muscle fiber immaturity
  Many small muscle fibers stain for alkaline phosphatase
  Many small & large muscle fibers are type 2C

ATPtase pH 4.3 stain

SRP MYOPATHY: MYOFIBER BASAL LAMINA PATHOLOGY

Laminin-α2 stain
SRP Muscle fiber basal lamina: Thickened & Irregular on large & smnall fibers

Control Muscle fiber basal lamina

Laminin-α2 stain

SRP: LATE, SEVERE PATHOLOGY, Months

Muscle fiber sizes: Varied; Small to Mildly large
Small muscle fibers: Rounded; Large nuclei; Basophilic cytoplasm
Endomysial connective tissue: Increased, Moderate to Marked
Pathology distribution: Patchy; Some regions with more endomysial connective tissue & only small rounded muscle fibers

H&E stain

H&E stain

Increased endomysial connective tissue
Hypertrophic and small muscle fibers

Gomori trichrome stain

Many small rounded muscle fibers
Increased endomysial connective tissue

H&E stain

Marked increase in endomysial connective tissue
Disease course of only 6 months

H& E stain

Gomori trichrome stain
Marked increase in endomysial connective tissue

VvG stain


ATPase pH 4.3 stain
Many muscle fibers retain immature features
  Type 2C on ATPase pH 4.3 stain
  Cytoplasm staind for alkaline phosphatase

Alkaline phosphatase stain

Histiocytic (red) staining of endomysial connective tissue

Acid phosphatase stain

MHC Class I
  Normal on muscle fibers
  Positive stained endomysial cells

MHC Class I stain


Laminin-α2 stain
Muscle Fiber Basal lamina: Thickened & Irregular (Above) vs control (Below)

Laminin-α2 stain

SRP: LATE, MILD PATHOLOGY, Months


H&E stain
Muscle fiber sizes: Varied; Small angular fibers, Scattered
Small muscle fibers: Angular; Basophilic cytoplasm
Endomysial connective tissue: Increased, Mild

H&E stain

VvG stain

Histiocytic cells: Scattered in endomysium

Acid phosphatase stain


ATPase pH 4.3 stain
Many muscle fibers retain immature features
  Type 2C on ATPase pH 4.3 stain
  Cytoplasm staind for alkaline phosphatase

Alkaline phosphatase stain


C5b-9 stain
Necrotic muscle fibers: Scattered (with C5b-9 stained cytoplasm)
MHC Class I: Not prominent on muscle fibers

MHC Class I stain

Neuromuscular junctions: Normal

Esterase stain

SRP MYOPATHY: CAPILLARY PATHOLOGY

Ulex europaeus agglutinin I stain
SRP myopathy
  Endomysial capillaries: Large & Mildly reduced in number
  Some muscle fibers have no adjacent capillary

Ulex europaeus agglutinin I stain
SRP myopathy
  Endomysial capillaries: Large
 

Ulex europaeus agglutinin I stain
Normal muscle
  Endomysial capillaries: Small
  All fibers have adjacent capillaries

Ulex europaeus agglutinin I stain

SRP MYOPATHY: MEMBRANE ATTACK COMPLEX (C5b-9)
  In cytoplasm of scattered necrotic muscle fiber
  On some capillaries

Antibody vs C5b-9
C5b-9
Deposition in endomysial capillaries and
  necrotic muscle fiber cytoplasm (Arrow)

Antibody vs C5b-9
C5b-9
Irregular deposition in endomysial capillaries (Arrows)

Return to Inflammatory myopathies
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4/30/2016